Cholera (Vibrio cholerae): evolution of a pandemic

Bacterial genomics of 19th century cholera in North America

Team members involved: Alison Devault
Project also in collaboration with Joseph Tien, David Earn, David Fisman, Anna Dhody of the Mütter Museum
Funding provided by: CIHR (Canadian Institutes of Health Research)

During the 19th century, cholera outbreaks killed millions of people across the globe. Caused by the bacterium Vibrio cholerae and spread through contaminated water sources, this diarrheal illness devastated crowded port cities like London and Philadelphia. While cholera has since been mostly eliminated from much of its historic range, major outbreaks still emerge in crowded, poverty-stricken, or disrupted areas of the world. Many of these outbreaks bring unique epidemiological challenges due to lack of acquired immunity in such populations.

It is generally assumed that 20th century improvements to sanitation and infrastructure limited cholera’s widespread geographic range that was seen in 19th century pandemics. It is also assumed that all 19th century cholera outbreaks are caused by the O1 Classic pathogenic V. cholerae strain, as was found in the late 19th and early 20th centuries. But this remains untested. Was historical cholera an as-yet unknown strain, having emerged independently of modern strains? Did it have a unique physiology, perhaps partially explaining its differing epidemiological characteristics and global pattern? To answer these questions, we aim to study the genome of this deadly pathogen by employing the most cutting-edge techniques in ancient DNA retrieval and sequencing.

Since pathogenic cholera cells only colonize the intestinal lining during infection (and never actually enter the bloodstream), it would be extremely unlikely that cholera DNA could be retrieved from archaeological skeletal remains. But rare historical medical intestinal samples, preserved in alcohols since the 1800s, offer a unique potential repository of historical cholera. By coupling targeted enrichment techniques and high-throughput sequencing, we will extract cholera virulence gene sequences from the complex pool of human and other bacterial DNA that dominate these specimens. In addition to being a significant technical achievement, this research promises to clarify the unique epidemiological features of historical cholera and therefore aid in understanding how and why pathogenic strains continue to emerge today.